ESPE Abstracts (2019) 92 P3-217

Clinical and Molecular Spectrum of Patients with Disorders of Sex Development: A Single Center Experience

Samim Özen1, Aysun Ata2, Hüseyin Onay 3, Selin Uzun 4, Damla Gökşen 1, Ferda Özkinay 5, Nazli Burcu Özbaran6, İbrahim Ulman 7, Şükran Darcan1


1Ege University School of Medicine Department of Pediatric Endocrinology, Izmir, Turkey. 2Ege University School of Medicine Department of Pediatric Endocrinology, Izmir, Turkey. 3Ege University School of Medicine Department of Medical Genetics, Izmir, Turkey. 4Ege University School of Medicine Department of Pediatrics, Izmir, Turkey. 5Ege University School of Medicine Department of Pediatric Genetics, Izmir, Turkey. 6Ege University School of Medicine Department of Pediatric and Adolescent Psychiatry, Izmir, Turkey. 7Ege University School of Medicine Department of Pediatric Urology, Izmir, Turkey


Introduction: Disorders of sex development (DSD) constitute a group of congenital conditions that affect urogenital differentiation and are associated with chromosomal, gonadal and phenotypic sex abnormalities.

Objective: To evaluate clinical and genetic features of childhood DSD cases.

Materials and Methods: DSD patients followed up between the years of 1981-2018 were evaluated in terms of their complaints, demographic, clinical features and genetic diagnoses.

Results: Out of 250 patients, 136(54%) were classified as 46, XY DSD, 59(%24) as 46, XX DSD and 54(22%) as sex chromosomal DSD. The median age at admission was 5,2(0-19) years. Molecular diagnoses was made in 121 of the patients (48%). The distribution of the molecular diagnosis of the 47(34,5%) 46 XY DSD patients were; 13(27%) SRD5A2, 7(14%) HSD17B3, 6(13%) AR, 3(6,3%) AMHR2, 2(4,2%) LHCGR, 2(4,2%) WT-1, 2(4,2%) HSD3B2, 2(4,2%) CYP17A1, 1(2,1%)SRY,1(2,1%) AMH and 1(2,1%) DHCR7. One patient had Y microdeletion. Two new suspected genes were detected by whole exome sequence analysis, which could be associated with ambiguous genitalia. One of them is homozygote c.332delC mutation in CCDC60 gene. The other is homozygote c.36_41dupGGAGGC mutation in ZNF653 gene. Forty nine of the 46, XX DSD patients were diagnosed with clinical and laboratory findings. 24(%40,6) of them was 21-hydroxylase deficiency, 9(15,2%) Mayer-Rokitansky-Küster-Hauser syndrome, 4(6,7%) 11-β hydroxylase deficiency, 4(6,7%) gonadal dysgenesis, 2(3,4%) aromatase deficiency, 2(3,4%) uterus anomaly, 1(1,7%) cloacal anomaly, 1(1,7%) vaginal agenesis, 1(1,7%) pregnancy related luteoma and 1(1,7%) ovotesticular DSD.In 46, XX group pathogenic mutations was detected in 20(33,8%) of the patients. Of these 16(80%) was CYP21A2, 1(5%) CYP11B1, 2(10%) CYP19A1 gene mutations and 1(5%) was SRY+ gonadal dysgenesis. Fifty-five (24%) of the patients were diagnosed as sex chromosomal disorder. Of these 39(72,2%) were Turner Syndrome, 3(5,5%) Klinefelter Syndrome, 10(18,5%) mix gonadal dysgenesis, 1(1,8%) 47 XXX and 1(1,8%) 47 XYY.All of the patients who decided gender change chose chromosomal sex (2 patients 46, XX, 8 patients 46, XY). 3(30%) of them was 5α-reductase deficiency, 1(10%) 17 β hydroxysteroid dehydrogenase-3 deficiency, 1(10%) 21-α hydroxylase deficiency and 1(10%) 3-β hydroxysteroid dehydrogenase deficiency.Malignant and pre-invasive gonadal malignancy were diagnosed in 8 patients.

Conclusion: Etiology of many DSDs are still cannot be established and they are arising due to complex genetic mechanisms.

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